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Dendrimer-functionalized Magnetic Nanoparticles for Peptide and Gene Delivery

The human body is a thing of wonder. However, the wonder is lost on the overwhelming majority of the human race. Most of us, after all, go through life completely unaware of what goes on within our own bodies. Did you know, for instance, that every organ in your body is being constantly and continuously destroyed and regenerated? Hard to believe, but true nevertheless.

How, you might well ask, could parts of your body be constantly destroyed without your feeling a thing? The answer is that the whole process happens at the cell level, and at a slow and steady pace. Cells in every organ in your body are programmed to divide themselves, thereby making brand new copies continuously. In doing so, each cell becomes part of the process of growth through multiplication.

In order to make sure that this doesn't result in an uncontrolled growth of the organ, however, each cell is also programmed to self-destruct after a prescribed lifetime. These two processes of the creation of new cells the destruction of old ones is orchestrated by the blueprint stored in our genes. The body, therefore, apparently remains the same because the processes of creation and destruction balance and cancel each other out.

At least, that is the case when all is going well. Sometimes, however, this system is thrown off balance. The self-destruct mechanism fails and the multiplication goes on unhindered. The result is an uncontrolled growth of tissue, referred to as a tumor.

n many cases the growing tissue is self-contained and doesn't affect any other organ or process in the body. These are called benign tumors. In other cases, tumors become malignant, invading and spreading the disruption in the cell life cycle to other tissues and organs in the body. The result is a state of cancer

Conventional management of cancer has focused on destroying or removing the malignant tissue by means of surgery, chemotherapy, radiation etc. While effective in their own way, each of these has limitations and side effects. The quest continues, therefore, to find a complete, foolproof and safe cure for cancer.

Gene therapy involves introducing genetic elements -- DNA strands, into the diseased cells to counter genetic damage or mutations that cause conditions such as cancer. While holding great promise, it also poses great challenges, such as how to deliver the therapeutic material safely and precisely to the target location.

The human body has many layers of defenses, each of which is designed to thwart perceived invasions. As a result, every foreign object is treated as something to be defended against, even if said foreign object is trying to help the body's defenses. This means that any vehicle for delivering a cure to a specific area has to find ways to deceive or overcome the body's natural resistance, while ensuring little or no damage to the body.

Some of the techniques currently in use involve the creation of pores in the membrane that covers the cell so that the therapeutic material may be slipped through. These methods, which use electricity, ultrasound etc, while effective in enabling the insertion of material into the cell, pose the hazard of compromising the integrity of the membrane.

At IITB-Monash, researcher Saumya Nigam has come up with a strategy to address this quandary. Guided by Prof. Dhirendra Bahadur of IIT Bombay and Dr. Qizhi Chen of Monash University, Australia, Saumya is working to develop a dendrimer-modified superparamagnetic iron oxide nanoparticles to be used as a nanovehicle to precision-deliver therapeutic cargo of to targeted cancer sites.

The IITB-Monash Research Academy is a Joint Venture between the IIT Bombay, India and Monash University, Australia. Opened in 2008, the IITB-Monash Research Academy operates a graduate research program located in Mumbai that aims at enhancing research collaborations between Australia and India. Students study for a dually-badged PhD from both institutions, and spend time during their research in both India and Australia.

Dendrimers are organic molecules whose structure resembles that of a Calliandra or powder-puff flower, with strings of atoms like branches arranged more or less symmetrically around a core. Characteristically, the behavior of these molecules is determined by functional groups on the surface of the ball-like molecules. Each of these functional groups can be tailored according to the requirement.

Superparamagnetism is a phenomenon observed in ferro- or ferri- magnetic materials in which, characteristically, the reduction of size to nanoscale results in zero coercivity and remanance in the absence of external magnetic field. If these particles are placed in an alternating magnetic field, power loss is observed in the form of heat which causes the temperature of the surrounding medium to rise.

Used judiciously, superparamagnetic nanoparticle can ease the passage of therapeutic material through the plasma membrane without damage to either. Furthermore, by using an external magnetic field to control the nanovehicle, the therapeutic material can be guided precisely to the cancer site with no damage to surrounding tissue. The genetic therapeutic material can then intercede into the dysfunctional cell life cycle and re-activate the cell self-destruct function.

While the therapeutic material can go a long way towards reducing the population of cancer cells, gene therapy by itself has not been able to achieve 100% destruction of cancer cells till date. The beauty of Saumya's solution is that the very nanovehicles that deliver the therapeutic material to the cancer site can further be used to achieve complete destruction of the cancer.

A carrier molecule for delivering therapeutic material has been successfully fabricated already. Saumya is now working to optimize its effectiveness in delivering genetic material to cancer cells. The nanoparticles to be used as the delivery vehicles, too, have been successfully created. What remains now is to combine gene therapy with heat treatment or hyperthermia.

Also, the iron oxide nanoparticles could be used as a dual modality imaging agent. The magnetic behavior of these nanoparticles results in longitudinal and transverse relaxation in the presenc of external magnetic field. The property could be utilized in the Magnetic Resonance Imaging of the tumor. Thus, these dendrimer-modified iron oxide nanoparticles could serve multiple functions in the diagnosis and therapeutics of cancer.

Graduate research scholars of IITB-Monash Research Academy study for a dually-badged PhD from both IIT Bombay and Monash University, spending time at both institutions to enrich their research experience. IITB-Monash Research Academy is a collaboration between India and Australia that endeavours to strengthen scientific relationships between the two countries.

Research scholar: Saumya Nigam, IITB-Monash Research Academy

Project title: Dendrimer-functionalized Magnetic Nanoparticles for Peptide and Gene Delivery

Supervisors: Prof. Dhirendra Bahadur & Dr. Qizhi Chen

Contact details: saumya.nigam@iitb.ac.in

For more information and details on this technology, email research@iitbmonash.org



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